tbuckley/cabot-search huggingface dataset:
PB1807: OUTCOME OF CORE BINDING FACTOR ACUTE MYELOID LEUKEMIA IN CHILDREN AND ADOLESCENTS: A SINGLE CENTER EXPERIENCE
Authors: N. Ben Sayed, G. Abichou, E. Bouselema, H. Regaieg, Y. Ben Youssef, A. Khelif
Journal: HemaSphere (2022)

Background: Core binding factor acute myeloid leukemia (CBF-AML) is a subgroup of AML, mainly defined by two gene rearrangements affecting CBF;t (8; 21)/RUNX1-RUNX1T1 and inv (16)/CBFB-MYH11. CBF-AML is considered as a favorable cytogenetic group. However, one-third of these patients relapse succeeding treatment. Aims: The main of this study is to evaluate the clinical characteristics and the outcome of this group of patients in our center. Methods: This retrospective study included all CBF-AML diagnosed between 2002 and 2020 in the hematology department of the University Hospital of Sousse. Patients were aged 20 years or less. The diagnosis was confirmed according to the WHO classification of hematological malignancies based on cytology and immune-phenotyping. An initial karyotype during diagnosis was performed in all the cases to classify the cases according to the prognostic MRC classification. Patients were treated by the standard chemotherapy regimen. Promyelocytic leukemia and secondary leukemia were excluded. Statistical analysis was performed using the Kaplan Meier method. Results: Among the 66 children and adolescents diagnosed with AML 15 had CBF AML (23%). 60% were male. The median age was 9 years (3-16). WBC at diagnosis was<4000 in 5 cases, 4000-10000 in 2 cases, between 10000-50000 in 7 cases, and >50000 in 1 case. Disseminated intravascular coagulation was noted in 2 cases. Twelve patients had t(8,21) and 3 patients had inv(16). 75% achieved complete remission after induction. 2 patients had a refractory disease (12,5%). Treatment-related mortality was 12,5% and meantime to relapse was 6,2 months in 5 patients (45%). Three patients responded to salvage chemotherapy (60%) and 2 died (40%). Hematopoietic stem cell transplantation (HSCT) was performed in only 2 patients. For the 3 others, HSCT was not feasible because of the absence of compatible matched related donors. The 5-year overall survival and relapse-free survivals were 55,7% and 58,3% respectively. Summary/Conclusion: Compared to the literature, the frequency of CBF-AML and epidemiological features were very similar. Furthermore, the majority had t (8, 21) in karyotype. Complete remission rate was slightly lower in our study (73% vs 85-96%), Treatment-related mortality was higher (12% vs 3-10%) which may be explained by the absence of protective isolation in the earlier years of the study. Regrettably, PFS was inferior to data from the literature (70-80%). The early use of stem cell transplants could improve our results.
P920: EFFECTIVENESS AND SAFETY OF SELINEXOR-BASED REGIMEN IN THE TREATMENT OF RELAPSED AND REFRACTORY MULTIPLE MYELOMA: A MULTICENTER REAL-WORLD STUDY FROM CHINA
Authors: L. Kuang, B. Fang, W. Chen, A. Liu, C. Li, L. Bao, C. Fu, J. Chen, H. Li, Y. Pang, A. Liao, Y. Liang, Y. Wei, J. Li
Journal: HemaSphere (2022)

Background: Selinexor is the first approved oral selective nuclear exportin inhibitor. Clinical trials have shown that selinexor-based regimens improved the survival of RRMM patients. However, there are limited reports on the effectiveness and safety of selinexor in the real world. Aims: To evaluate the effectiveness and safety of selinexor-based regimens in the treatment of patients with relapsed and refractory multiple myeloma (RRMM) in real world settings. Methods: The clinical data of 53 patients with RRMM who were treated with selinexor-based regimens in 11 centers in China from July 2020 to December 2021 were retrospectively analyzed, and the response, survival and side effects were evaluated. Results: The median age of the 53 patients with RRMM at the time of treatment with the selinexor-based regimens was 60 years (range: 41-79). The median time since initial diagnosis was 30 months (range: 1-156). The median number of prior lines of therapy was 4 (range: 1-11), including 22 (41.5%) cases who had received autologous hematopoietic stem cell transplantation in the past, 8 cases (15.0%) who had been exposed to CART, 34 cases (64.1%) who were double-class refractory (proteasome inhibitors and immunomodulators), and 20 cases (33.7%) who were triple-class refractory(proteasome inhibitors, immunomodulators and daratumumab). The number of patients with high-risk cytogenetics [17p-/t (14;16)/t (4;14)/1q21] at onset was 24 (66.7%), and 20 (55.6%) at the time of the lastest relapse. The responses were evaluable in 47 patients, and the overall response rate (ORR, ≥PR) was 44.7%, including 3 cases with CR (6.4%), 4 cases with VGPR (8.5%), and 14 cases with PR (29.8%). The median follow-up time was 2.75 months (range: 0.14-17.5). In the responders, the median time to first response was 1.07 months (range: 0.25-2.71), and the median duration of response (DOR) was 7.75 months (95% CI: 4.705-10.795). The median progression-free survival (PFS) was 6.107 months (95%CI: 2.856, 9.358), and the median overall survival (OS) had not been reached. The major grade 3-4 adverse effets were hematological toxicity, and the incidences of grade 3-4 neutropenia, lymphopenia, and thrombocytopenia were 41.2%, 37.9%, and 53.0%, respectively. The incidence of dose reductions of selinexor due to myelosuppression was 7.1%. Among the non-hematological adverse effects, the most common grade 3-4 adverse effects were nausea and vomiting (38.7%), fatigue (18.6%), and infection (18.6%). Image:Summary/Conclusion: In the real world, the selinesor-based regimens have good effectiveness and safety profile in the treatment of RRMM.
PB2045: POLYCYTHEMIA VERA IN YOUNG SUBJECTS: ABOUT A COHORT OF 11 CASES
Authors: S. Bougherira, S. Bentorki, F. Grifi
Journal: HemaSphere (2022)

Background: Polycythemia Vera (PV) is a typical Philadelphia-negative (Ph_) myeloproliferative disease. It is secondary in 95% of cases to the JAK 2 mutation on exon 14. The median age at diagnosis is 65 years. PV is unusual in young patients, so that little information is available on long-term clinical evolution in this particular group. Aims: The aim of this study is to describe the clinical presentation, biologic features, treatment approaches, and long-term outcome especially the risk of thrombosis. Methods: Of all the 64 patients followed in our department for PV, we report 11 cases aged less than 55 years. The inclusion criteria were a diagnosis satisfying the PVSG criteria and, from 2016 on, the WHO criteria. Secondary causes of erythrocytosis were carefully ruled out in all patients. At diagnosis, cytogenetic and molecular analysis were not done in our patients. Search for JAK2 mutation and serum EPO dosage were performed in all cases. Results: PV in young patients represents 17% of all PV followed. Median age of our population is 44 years, range 32-52, with 27% of patients under 40 years old. slightly more often in men with (sex ratio 1.75). Arterial hypertension is the most common comorbidity and it is a cardiovascular risk factor in the majority of patients. A thromboembolic event revealing PV is found in 2 patients. The main clinical signs were significant burning sensation in fingers and palms due to the increased blood viscosity, splenomegaly which observed in 63% of patients, and the occurrence of severe itching on contact with warm bath. Thromboembolic events occurred in 3 patients during the evolution. All patients had the diagnosis of absolute erythrocytosis with moderate hyperleukocytosis and thrombocytosis. Bone marrow biopsy showed hypercellular bone marrow with erythroid and megakaryocytic lineage hyperplasia. The JAK2 V617F mutation was positive with an average allelic load high at 63.1% [22.9 - 93.6]. The dosage of serum EPO was low with an average of 1 mU/ML. During the follow-up period, no patient had progression into acute leukemia or myelofibrosis with myeloid metaplasia, thus no death. The median survival is 49 months [3-99] and the survival without thromboembolic event is 42 months [3-99]. The majority of patients were treated by phlebotomy with 1 or 2 units per month, before starting hydroxy urea. The use of the latter in association with Aspirin (n=10 pts) reduced the use of bloodletting. The thrombotic events required treatment with antithrombotic drug. No patient was treated with Ruxolitinib (treatment not available). Summary/Conclusion: PV remains rare in patients under 55 years of age (17% in our cohort). This has an impact on overall survival and thromboembolic event-free survival with a good prognosis in the young population.
PB2169: METHYLATION OF P53-RESPONSIVE ONCOSUPPRESSIVE MICRORNA GENES IN DIFFUSE LARGE B-CELL LYMPHOMA TUMOR TISSUE
Authors: E. Voropaeva, T. Pospelova, M. Churkina, O. Berezina, A. Gurazheva, V. Maximov
Journal: HemaSphere (2022)

Background: Hsa-miR-203, hsa-mir-129, hsa-miR-34a, hsa-miR-34b and hsa-miR-34c are oncosuppressive microRNAs through which the antitumor activity of p53 is realized. Aims: To identify the frequency, specificity and clinical significance of MIR-34B/C, MIR-34A, MIR-203 and MIR-129-2 genes methylation in Diffuse Large B-cell Lymphoma (DLBCL). Methods: Methylation status of the genes in tumor tissue (n=73) was studied by methyl-specific PCR and methyl-sensitive analysis of high-resolution melting curves. DNA isolated from lymph node biopsies with reactive polyclonal B-cell proliferation (n=11) was used to control the tumor-specificity of the detected methylation. The quantitative analysis of the combined methylation of the studied genes was carried out with the calculation of the one-sided Fisher exact criterion (p-value) and the frequency of false discoveries (FDR) (q-value) was calculated using the Benjamin-Hochberg procedure. Results: Aberrant methylation of the promoters of the studied genes can serve as a significant mechanism for reducing the miR-34B/C, miR-34A, miR-203 and miR-129 micro-RNAs expression in the tumor tissue of DLBCL. It is occurs in combination and is tumor-specific. Thus methylation of MIR-129-2, MIR-203, MIR-34A and MIR34B/C in lymphoma samples occurred with a frequency of 67%, 66%, 27% and 62%, respectively, and there was no reactive lymph node tissue. Combined methylation of MIR-203, MIR-129-2 and MIR-34B/C genes (p<0.013, q<0.020), as well as pair of MIR-34B/C and MIR-34A genes (p=0.010, q=0.029) was detected.Methylation of MIR-34A was associated with an unfavorable prognosis according to the International Prognostic Index (p=0.002), and methylation of MIR-34B/C (p=0.026) and MIR-203 (p=0.011) was associated with a Ki-67 expression level of more than 45% in tumor tissue. Summary/Conclusion: Aberrant methylation of oncosuppressive microRNA genes associated with underlying p53 signaling pathways is a potentially useful molecular biomarker in the diagnosis, prognosis of tumors and the development of a strategy for targeted therapy of DLBCL.
PB1766: PROGNOSTIC SIGNIFICANCE OF ACTIVIN A IN ADULT EGYPTIAN PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA.
Authors: M. Azzazi, H. Hegab, A. EL-Ghammaz, V. Shawky, H. Hafez, R. Helal
Journal: HemaSphere (2022)

Background: Activin A belongs to the transforming growth factor-beta (TGFβ) superfamily of cytokines which exert a plethora of biological functions, including developmental differentiation, sex determination, control of cellular proliferation, migration and immune responses. Activins are dimeric glycoproteins that play a significant role in reproduction and in endocrine active tumors, although inhibins and activins have primarily been described in human gonads and identified as modulators of follicle-stimulating hormone production of the pituitary gland, they have also been detected in several solid tumor types, including endocrine-responsive endometrial, ovarian, and breast carcinomas. Their differential expression has suggested their important role in malignant cell transformation, as well as possible roles in cancer differentiation, proliferation, and growth tumors Aims: The aim was to assess expression of Activin A in the serum of adult patients with acute lymphoblastic leukemia and its influence on remission and survival of ALL patients. Methods: Serum Activin A was measured using ELISA in 30 acute lymphoblastic leukemia patients recruited from Hematology and Bone Marrow Transplantation Unit, Ain Shams University Hospitals and followed for 1 year in comparison to 15 healthy controls Results: Serum level of Activin A was elevated in acute lymphoblastic leukemia patients (ALL) in comparison to control group with a statistically significant difference (P<0.001).A statistically significant negative correlation was detected between age of the patients and Activin A level(P= 0.035). The comparison between different outcomes of the patients (Remitted, Relapsed and died patients) above and below the mean level of activin A (265.667 ng/ml),was statistically significant (P<0.001). A statistically significant negative correlation was detected between Activin A level in ALL patients and overall survival (OS) (P <0.001) and by using the log-rank test, a statistically significant difference (P <0.001) was detected in ALL patients above and below the mean level of Activin A. However, statistically nonsignificant difference was detected between the mean Activin A level in Philadelphia chromosome (Ph) positive patient and Ph negative patients (P= 0.839) Summary/Conclusion: Activin A can be a useful poor prognostic biomarker in acute lymphoblastic leukemia patients, also it can be used as a predictor for aggressiveness of the disease, resistance and survival.
Image Segmentation for MR Brain Tumor Detection Using Machine Learning: A Review
Authors: Toufique A. Soomro, Lihong Zheng, Ahmed J. Afifi, Ahmed Ali, Shafiullah Soomro, Ming Yin, Junbin Gao
Journal: IEEE Reviews in Biomedical Engineering (2022)

Magnetic Resonance Imaging (MRI) has commonly been used to detect and diagnose brain disease and monitor treatment as non-invasive imaging technology. MRI produces three-dimensional images that help neurologists to identify anomalies from brain images precisely. However, this is a time-consuming and labor-intensive process. The improvement in machine learning and efficient computation provides a computer-aid solution to analyze MRI images and identify the abnormality quickly and accurately. Image segmentation has become a hot and research-oriented area in the medical image analysis community. The computer-aid system for brain abnormalities identification provides the possibility for quickly classifying the disease for early treatment. This article presents a review of the research papers (from 1998 to 2020) on brain tumors segmentation from MRI images. We examined the core segmentation algorithms of each research paper in detail. This article provides readers with a complete overview of the topic and new dimensions of how numerous machine learning and image segmentation approaches are applied to identify brain tumors. By comparing the state-of-the-art and new cutting-edge methods, the deep learning methods are more effective for the segmentation of the tumor from MRI images of the brain.
P445: CRYPTIC TRANSLOCATION T(5;11)(Q35;P15) RESULTING IN NUP98::NSD1 GENE FUSION IN ADULTS WITH DE NOVO ACUTE MYELOID LEUKEMIA (AML)
Authors: S. Ransdorfova, J. Markova, M. Valerianova, J. Brezinova, M. Onderkova, I. Mendlikova, L. Lizcova, L. Pavlistova, K. Svobodova, S. Izakova, A. Jonasova, C. Salek, Z. Racil, Z. Zemanova
Journal: HemaSphere (2022)

Background: The NUP98::NSD1 fusion, a product of the cryptic translocation t(5;11)(q35;p15.5), is a recurrent genetic change in cytogenetically normal patients with AML. It occurs most frequently in children (16%) and young (2%) AML patients, very rarely in adult patients. The coexistence of internal tandem duplication of FLT3 gene (FLT3::ITD) found in more than 70% of NUP98::NSD1 positive patients is always associated with a poor prognosis and results in high frequency of induction failure. Aims: The aim of this study was to determine the incidence of the NUP98::NSD1 fusion gene in adults with AML and NUP98 rearrangement. Methods: We examined the bone marrow cells of 268 newly diagnosed AML patients using conventional karyotyping in combination with FISH (Abbott, MetaSystems) and mFISH/mBAND (MetaSystems). We used RT-PCR followed by direct sequencing to detect fusion genes. We processed the PCR product by ExoSAP-IT and directly sequenced on ABI Prism 310 genetic analyzer using the Big Dye Terminator kit v. 3.1. Results: In nine out of 268 cases we identified rearrangement of the 11p13-15 region. We confirmed t(5;11)(q35;p15.5) with NUP98::NSD1 gene fusion in four of them (4/268; 1.5%). Sequence analyses proved the NUP98-NSD1 transcript, arising from fusion of NUP98 exon 12 with exon 6 in NSD1 gene, in all four patients (2M/2F; FAB M4/M5b; age 42, 54, 64 and 64 years). FLT3::ITD mutation was detected in all of them. Specific primers and a probe have been designed to monitor minimal residual disease during therapeutic treatment of the patients. Out of 4 patients, two died (median OS 9 months) and two patients are alive (4 and 1 year after allogenic bone marrow transplantation). Summary/Conclusion: Our study demonstrated the occurrence of t(5;11)(q35;p15.5) with NUP98::NSD1 gene fusion also in adults over 60 years of age. We confirmed the NUP98::NSD1 fusion gene in 1.5% adults AML patients. With respect to the poor prognosis of the patients with NUP98::NSD1 fusion gene, we suggest pre-screening of NUP98 gene rearrangement using FISH in cytogenetically normal AML patients with confirmed FLT3::ITD mutation. Supported by MH CZ-DRO-VFN64165, DRO-UHKT00023736.
PB2180: EPIDEMIOLOGICAL CHARACTERS OF ADULT EGYPTIAN STEM CELL TRANSPLANT PATIENTS: A SINGLE CENTER EXPERIENCE
Authors: M. Elbogdady, S. Shamaa, M. Nasr, M. Elzaafarany, T. Elkhodary, M. Abd Elhamid, E. Azmy, M. Awad, H. Ghazy, M. Elbayomy, M. Taalab, S. Saber, Z. Emarah, M. Denwar, A. Elsergany
Journal: HemaSphere (2022)

Background: Stem cell transplanrt is an integral part of the treatment of hematologic disorders and especially malignant ones. Egypt which has a population around One hundred and five million people has a limited number of stem cell beds not exceeding 100 beds allover the country which is very low compared to international standards. Aims: The aim of this study is to describe the epidemiological situation of adult Stem cell transplant patients in Mansoura, Egypt as basedon retrospective analysis of our electronic clinical records at hematology unit Oncology center mansoura university(OCMU) between November 2019 and February 2022 in our freshly established stem cell unit which started operating on November 2019. Methods: Adult patients who underwent stem cell transplant were recruited from stem cell transplant unit at OCMU from November 2019 to February 2022.Demographic characteristics, clinical history, and laboratory and treatment data were collected. Results: The study included 55 recorded patients who underwent Stem cell transplant at OCMU from November 2019 to February 2022. All cass came from delta region 70 % from Dakahlia governorate. Male patients represented 47.3% (26) while female 52.7% (29). We Had only 2 cases of Allogenic stem cell transplant while the remaining 53 were Autologus.The mean age undergoing SCT was 34.7 years with the minimum and the maximum being 22 & 66 years. 40% (22) had NHL, 29.1% (16) had HD, 27.3% had MM and 1.8 % (1) had AML & ALL respectively. Most cases were transplanted in CR2 or more for Lymphoma except for 3 in CR1 being highly refractory or aggressive. MM cases were at least in VGPR and 2 cases of plasma cell leukemia were transplanted. Acute leukemia who underwent allogenic were in CR2 for ALL & CR3 for AML. The used conditioning regimen was BeEAM for lymphoma, High dose melphalan for MM, Bu/Cy for Allogenic. Summary/Conclusion: Stem cell transplant is still not feasible to all leigable candidates due to shortage of facilities and trained personnel especially in developing countries. establishement of new SCT units wil help provide a more convinient obtion for those who require such a procedure
P1666: EFFECT OF AGONISTS TO THROMBOPOIETIN RECEPTORS ON PLATELET GLYCOME OF PATIENTS WITH IMMUNE THROMBOCYTOPENIA
Authors: E. Monzón Manzano, M. T. Alvarez Román, P. Acuña, E. G. Arias Salgado, A. Ramírez, M. Martín Salces, M. I. Rivas Pollmar, A. González Ceberino, N. V. Butta, V. Jiménez Yuste
Journal: HemaSphere (2022)

Background: Platelet destruction and suppression of platelet production are involved in immune thrombocytopenia (ITP). Recently, attention has been drawn to the composition of platelet glycome in etiopathogenesis of ITP. We have previously reported that exposure of glycosides that might be involved in platelet destruction are increased in platelets from ITP patients (Figure 1A). Agonists to thrombopoietin receptors (TPO-RAs) have been shown to produce sustained platelet responses in ITP. Nevertheless, little is known about the effect of TPO-RAs on platelet’s features. Aims: We aimed to study whether the treatment with TPO-RAs modified platelet function and glycoside composition of platelets from ITP patients Methods: ITP patients were studied before and after achieving a response (defined as a platelet count ≥30×109 platelets/L and at least two fold increases over the baseline count) to TPO-RA therapy. Platelet activation markers (activation of fibrinogen receptor determined through PAC1-binding, and TRAP-induced P-selectin and CD63 exposure) and active caspase-3, -7, -8 or -9 were evaluated. Platelet surface glycan exposure was analysed by determining the binding of lectins to specific glycosidic residues. Samples were analyzed by flow cytometry. Results were expressed as the ratio between values obtained after responding/before treatment with TPO-RA. Results: 16 patients were included [53.8% women, 58 (22–81) years, 46.2% with eltrombopag, 53.8% with romiplostim]. Increment of platelet count was variable and was accompanied by the recovery of platelet´s ability to be stimulated, especially the activation of fibrinogen receptor. TPO-RA treatment seemed to have a negligible effect on caspase activity. Regarding glycoside residues, exposure of ɑ-mannose, galactose and ß-GlcNAc showed a tendency to decrease (Figure 1). Image:Summary/Conclusion: Our results showed that TPO-RA treatment appeared to recover platelet function and to restore a glycome composition similar to that found in a healthy state.
Hydrodynamic Modeling and Parameter Identification of a Bionic Underwater Vehicle: RobDact
Authors: Qiyuan Cao, Rui Wang, Tiandong Zhang, Yu Wang, Shuo Wang
Journal: Cyborg and Bionic Systems (2022)

In this paper, the hydrodynamic modeling and parameter identification of the RobDact, a bionic underwater vehicle inspired by Dactylopteridae, are carried out based on computational fluid dynamics (CFD) and force measurement experiment. Firstly, the paper briefly describes the RobDact, then establishes the kinematics model and rigid body dynamics model of the RobDact according to the hydrodynamic force and moment equations. Through CFD simulations, the hydrodynamic force of the RobDact at different speeds is obtained, and then, the hydrodynamic model parameters are identified. Furthermore, the measurement platform is developed to obtain the relationship between the thrust generated by the RobDact and the input fluctuation parameters. Finally, by combining the rigid body dynamics model and the fin thrust mapping model, the hydrodynamic model of the RobDact at different motion states is constructed.